That cholinergic activity in the septal-hippocampal pathway is involved in extinction was directly demonstrated by comparing the acetylcholine turnover rate (TRACh) in the rat hippocampus with extinction of a food reinforced lever press response after intraseptal injection of the GABA agonist muscimol. Doses (.3 to 3 nmoles) which decreased the TRACh also increased the response rate during extinction. Responding during the continuous reinforcement (CRF) schedule prior to extinction was also increased but to a lesser extent. Higher doses (10-30 nmoles) further decreased the TRACh and were accompanied by sedation. The TRACh in the hippocampus was also measured in drug-free rats undergoing extinction after training on a CRF or variable interval 60 seconds (VI-60) reinforcement schedule. Although the VI-60 rats responsed more than the CRF rats during extinction, there were no differences between the TRAChs. These results indicate that muscimol-induced decreases in hippocampal TRACh are accompanied by interference with extinction, but that operantly-induced differences in this behavior are not accompanied by large changes in TRACh. We are currently investigating whether the relationship between TRACh and operant behavior after muscimol is causally related.